Unraveling the genetic mysteries of vision loss

More than 5 million people worldwide have inherited retinal diseases that can lead to significant vision loss or blindness. Great strides have been made to identify the genetic mutations responsible for many of these conditions, but for about 25% of the disorders, the cause remains a mystery — one that molecular geneticist Rui Chen, PhD, aims to solve.

Chen recently joined UC Irvine as a professor of ophthalmology after more than 20 years at Baylor College of Medicine in Houston, Texas, where he earned his doctorate and completed a post-doctoral fellowship in genetics, focusing on the retina’s DNA. In 2019, he was among a team of national experts tapped to map the human retina and all of its cells for the Human Cell Atlas, a $68-million international project funded by the Chan Zuckerberg Initiative.

Chen’s expertise will significantly enhance UC Irvine’s Center for Translational Vision Research and a new Program in Precision Genome Editing, where he now  leads a project to pinpoint every genetic cause of inherited retinal diseases.

For Chen, the eye is the ideal focus for genetic study: it’s complicated enough to inspire a lifelong fascination, yet small enough to be a manageable research target. “The eye system is almost like a mini brain,” he says. In the early years of genetic testing for eye conditions, Chen’s lab helped develop DNA panels to give patients a clearer understanding of their prognosis — whether they would gradually lose vision over decades or experience more rapid changes. With those tests now widely available, he has turned his attention to identifying genetic mutations that have yet to be discovered.

Not every gene implicated in inherited retinal disease drives the condition. Chen uses mice and lab-grown retinal cells to study suspected mutations and determine exactly which ones cause specific types of vision loss. Once identified, the genes can be targeted for new treatments, including future gene-editing therapies.

Ultimately, Chen envisions establishing a genetic program that would develop clinical trials to benefit patients at the UCI Health Gavin Herbert Eye Institute.

While most genetic eye mutations are found around the globe, some are limited to specific populations. For example, one RP1 gene mutation, which leads to an aggressive, early-onset form of retinitis pigmentosa, occurs exclusively among individuals of Kuwaiti descent. Chen is working to develop gene-editing therapies specifically targeting this group as part of his broader research, exemplifying the principles of precision medicine.

Already, patients from around the world seek Chen’s expertise, hoping his research may lead to new treatments for their condition. Because many of these diseases affect only a small number of people, they are often overlooked by pharmaceutical companies. Instead, these patients rely on academic medical researchers to find answers and possible therapies. To support these individuals, Chen frequently helps them create patient support groups to raise awareness of their shared condition and explore more research opportunities.

For people with more advanced vision loss for whom gene-editing therapies will not be an option, Chen is exploring regenerative medicine pathways with grant funding from the Foundation for Fighting Blindness.

“In cases where the disease has progressed to the point where the patient no longer has photoreceptor cells to target with gene therapies, we are pursuing some very interesting leads to regenerate neurons that may have wonderful success,” Chen says.

Chen’s research team will eventually move into the Falling Leaves Foundation Medical Innovation Building. There, he expects his work on the genetic causes of inherited retinal diseases to be amplified by collaborations with other vision scientists also pursuing bench-to-bedside research.

Together, he hopes they will find therapies for the millions of people affected by vision loss.